The insulin-like growth factors (IGFs) signaling system has been shown to play important roles in neoplasia. Insulin-receptors (IR) belong to the IGF signaling network. IGF receptor type 1 (IGF-IR) and its ligands (IGFI and II) are over-expressed in many types of solid and hematopoietic malignancies, including prostate cancer, breast cancer, liver cancer, and colon cancer, etc. There is substantial experimental and clinical evidence that targeting IGF-IR is a promising therapeutic strategy against cancer.
Strategies for down-regulating the IGF signaling system include reducing ligand bioavailability and inhibiting receptor function. Inhibition of IGF receptor function can be achieved using receptor-specific antibodies or small molecule tyrosine kinase inhibitors. Desired IGF-IR-specific neutralizing antibodies can not only inhibit IGF-IR function, but also block the IGF-IR-mediated signaling pathway. There is a need to develop IGF-IR-specific antibodies that can inhibit cell-surface IGF-IR and block the binding of IGF-IR ligands to IGF-IR, thereby inhibiting ligand-induced receptor phosphorylation and the downstream signaling. IGF-IR-specific antibodies without cross-reactivity with IR are particularly desired.